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GSE25613
Homo sapiens
19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL.
Publication Title
A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Notably, deletion or uniparental disomy of chromosome 7q were detected in 39% of SMZLs but in only 9 of 170 (5%) mature B-cell lymphomas (p<10-6). The presence of unmutated IgVH genes, genomic complexity, 17p13-P53 deletion and 8q gain including MYC gene, but not 7q deletion, were correlated with shorter overall survival. Extensive mapping analyses narrowed down the commonly deleted region to 2.7 Mb. in 7q32.1-q32.2 from SND1 to COPG2 genes. High-throughput sequencing analysis of the 7q32 deleted segment in SMZL cells did not identify bi-allelic deletions, insertions or clear pathogenic mutations, but detected six single nucleotide changes in IRF5 (n=2), TMEM209 (n=2), CALU (n=1) and ZC3HC1 (n=1). Comparative expression analysis found that IRF5, TMEM209 and CALU genes had down-regulated expression in lymphomas with 7q32 deletion vs. non-deleted tumors. Ectopic expression of IRF5 in marginal-zone lymphoma cells decreased cell proliferation and induced apoptosis. These results indicate that small deletions, insertions and/or point mutations inactivating genes within 7q32 are not common events in SMZL. Further studies are required to evaluate the putative role of IRF5 in SMZL pathogenesis.
Publication Title
High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Sample Metadata Fields
Disease, Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Gene expression in S2 cells after CG9740 or CP190 RNAi
Publication Title
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
The transcription factor Nkx2.5 is required for specification of pharyngeal arch second heart field (SHF) progenitors that contribute to outflow tract (OFT) and right ventricle (RV) formation. Multiple sets of microarray data were analyzed to identify genes that are candidate targets of Nkx2.5 in the second heart field. These sets are: 1) publicly available data for cardiothoracic tissue from E9.5 Nkx2.5 wild-type, heterozygous and homozygous embryos; 2) an analysis of mouse E10.5 pharyngeal arch tissue; 3) an analysis of mouse E12.5 heart tissue; and 4) a temporal analysis of the cardiogenic cell line P19CL6. This combined analysis identified 11 genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF-containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5 expression.
Publication Title
Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pluripotent P19CL6 embryonic carcinoma cells can be differentiated to a cardiac lineage by culture in the presence of DMSO. The goal of this study was to characterize temporal gene expression patterns associated with cardiogenic differentiation. Gene expression analysis was conducted on differentiating P19CL6 cells at several time points following induction with 1% DMSO. Samples were processed for analysis by Affymetrix GeneChip.
Publication Title
Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Assessing relevant differences between human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells is important, given that such differences may impact their potential therapeutic use.
Publication Title
The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Assessing relevant differences between human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells is important, given that such differences may impact their potential therapeutic use.
Publication Title
The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples